SDH-B, INSM1, and GATA3 expression in cauda equina neuroendocrine tumors: report on 21 cases from a North indian tertiary care center.

Primary neuroendocrine tumors (NETs) of the central nervous system are rare, primarily seen in the cauda equina region, known as cauda equina NETs. This study was carried out to evaluate the morphological and immunohistochemical characteristics of cauda equina NETs. All cases of histologically proven NETs that originated within the spinal cord from 2010 to 2021 were retrieved from the surgical pathology electronic database. For each case, the clinical presentation, site, radiological features, functional status, and preoperative diagnosis were recorded. Immunohistochemical stains for GFAP, synaptophysin, chromogranin A, cytokeratin 8/18, INSM1, Ki-67, GATA3, and SDH-B were performed for every case using an automated immunostainer. GATA3 immunohistochemistry was repeated manually. A retrospective probe of records revealed 21 cases of NETs having a mean age of 44 years and slight male dominance (M:F ratio: 1.2:1). Cauda equina was the most prevalent site of involvement (19, 90.5%). The most typical presentation was lower backache and weakness of bilateral lower limbs. The histopathological features were similar to NETs seen at other sites. Reactivity for at least one neuroendocrine marker was seen in all cases while GFAP was negative. Cytokeratin 8/18 was expressed in the majority (88.9%) of cases. INSM1 and GATA3 expression was seen in 20 (95.2%) and 3 (14.3%) cases, respectively. All cases retained SDH-B cytoplasmic staining. Higher Ki-67 index (≥3%) was associated with a higher risk of recurrence. Cauda equina NETs rarely express GATA3 and are unlikely to be associated with SDH mutations. Recurrent cases may be negative for synaptophysin, chromogranin, and cytokeratin; thus, INSM1 immunohistochemistry is helpful.

A Two-in-One Tumor in the Adrenal: A Functional Adrenocortical Adenoma with Myelolipomatous Differentiation.

BACKGROUND: Adrenocortical adenoma (ADA) and myelolipoma are two common benign neoplasms of the adrenal cortex that have been reported to occur together. CASE REPORT: A 14-year-old girl presented with the features of ACTH-independent endogenous Cushing syndrome. Abdominal CECT revealed a left adrenal 2.3 × 1.8 × 1.5 cm arterially enhancing nodular lesion with central hypodensity. Histologically, this was an ADA with oncocytic change and myelolipomatous differentiation/metaplasia. DISCUSSION/CONCLUSION: ADA with myelolipomatous differentiation/metaplasia can occur in the pediatric age group.

Assessment of risk of malignancy by application of the proposed Sydney system for classification and reporting lymph node cytopathology.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is one of the most commonly used techniques for evaluating lymphadenopathy. Recently, the Sydney system was proposed for assessing the performance, classification, and reporting of lymph node (LN) cytopathology. The present study was conducted to assess the risk of malignancy associated with each of the diagnostic categories of the proposed Sydney system. METHODS: This was a 2-year retrospective study of LN-FNAs; cytologic diagnoses were categorized by the proposed Sydney system. Cytological diagnoses were correlated with the corresponding histopathological diagnoses to assess diagnostic accuracy and risk of malignancy for each diagnostic category. RESULTS: Of 23,335 FNAs during the study period, 6983 (30%) were performed on LNs. Of these, 289 (4.1%) cases were reported as nondiagnostic/inadequate (L1); 3397 (48.6%) were reported as benign (L2); 33(0.5%) as atypical cells of undetermined significance (L3), 96 (1.4%) as suspicious for malignancy (L4) and 3168 (45.4%) as malignant (L5). Subsequent histopathology was available for 618 (8.8%) cases. On cytohistopathologic correlation, 552 (89.3%) were concordant and 66 (10.7%) discordant. The overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of LN-FNA were 79.9%, 98.7%, 98.4%, 83.1%, and 89.3%, respectively. The risk of malignancy was 27.5% for the nondiagnostic category, 11.5% for the benign, 66.7% for the atypical, 88% for the suspicious, and 99.6% for the malignant categories. CONCLUSIONS: FNAC has high diagnostic accuracy for the diagnosis of various LN pathologies. Application of the proposed Sydney system can help in achieving uniformity and reproducibility in cytologic diagnoses and also help in risk-stratification on cytology.

A fatal case of enterovirus infection with secondary hemophagocytosis-case report with review of literature.

Enterovirus is a common viral infection, which can affect multiple organ systems with an array of clinical presentation such as meningitis, encephalitis, myocarditis, and disseminated infections. The illness is usually asymptomatic and self-limited but few cases can be severe and life-threatening especially when associated with hemophagocytosis. We discuss a fatal case of disseminated enterovirus infection and the histomorphological features of the infection.

Mechanism of amorphous itraconazole stabilization in polymer solid dispersions: role of molecular mobility.

Physical instability of amorphous solid dispersions can be a major impediment to their widespread use. We characterized the molecular mobility in amorphous solid dispersions of itraconazole (ITZ) with each polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) with the goal of investigating the correlation between molecular mobility and physical stability. Dielectric spectra showed two mobility modes: α-relaxation at temperatures above the glass transition temperature (Tg) and ß-relaxation in the sub-Tg range. HPMCAS substantially increased the α-relaxation time, with an attendant increase in crystallization onset time and a decrease in crystallization rate constant, demonstrating the correlation between α-relaxation and stability. The inhibitory effect on α-relaxation as well as stability was temperature dependent and diminished as the temperature was increased above Tg. PVP, on the other hand, affected neither the α-relaxation time nor the crystallization onset time, further establishing the link between α-relaxation and crystallization onset in solid dispersions. However, it inhibited the crystallization rate, an effect attributed to factors other than mobility. Interestingly, both of the polymers acted as plasticizers of ß-relaxation, ruling out the latter's involvement in physical stability.

Molecular motions in sucrose-PVP and sucrose-sorbitol dispersions-II. Implications of annealing on secondary relaxations.

PURPOSE: To determine the effect of annealing on the two secondary relaxations in amorphous sucrose and in sucrose solid dispersions. METHODS: Sucrose was co-lyophilized with either PVP or sorbitol, annealed for different time periods and analyzed by dielectric spectroscopy. RESULTS: In an earlier investigation, we had documented the effect of PVP and sorbitol on the primary and the two secondary relaxations in amorphous sucrose solid dispersions (1). Here we investigated the effect of annealing on local motions, both in amorphous sucrose and in the dispersions. The average relaxation time of the local motion (irrespective of origin) in sucrose, decreased upon annealing. However, the heterogeneity in relaxation time distribution as well as the dielectric strength decreased only for ß1- (the slower relaxation) but not for ß2-relaxations. The effect of annealing on ß2-relaxation times was neutralized by sorbitol while PVP negated the effect of annealing on both ß1- and ß2-relaxations. CONCLUSIONS: An increase in local mobility of sucrose brought about by annealing could be negated with an additive.

Is relief from diabetes just a breath away?

Pulmonary insulin delivery is steadily emerging as a promising solution for the treatment of diabetes mellitus. The large as well as thin absorptive area of the lungs has not been explored until now for the treatment of systemic disease like diabetes. With an understanding of the lung anatomy and physiology and the transport mechanism of insulin through lungs, diabetic treatment through the pulmonary route may well become the reality of the 21(st) century. Though the transport of insulin through the lungs itself appears quite encouraging, potential problems concerning the formulation of a peptide like insulin in the form of an aerosol seem to be the most challenging. Stability aspects, stringent control of Mass Median Aerodynamic Diameter, antigenicity, insulin losses due to the device and impaction, sedimentation and diffusion in the nonabsorptive areas of the airway system (especially in the oropharynx) emerge as major concerns. This is in addition to the problems of lack of reproducibility of dose delivery by an inhaler where individual variations due to inspiratory differences and method of use of device come into play. Lung diseases and smoking may alter lung mechanisms and dose alterations are to be studied in such cases. Though almost equally effective, if not more, than the subcutaneous insulin route, even with proved short-term efficacy, insulin delivery through lungs is a potential but not a wholly proven means for blood glucose control.

Study of forced degradation behavior of enalapril maleate by LC and LC-MS and development of a validated stability-indicating assay method.

In the present study, comprehensive stress testing of enalapril maleate was carried out according to ICH guideline Q1A(R2). The drug was subjected to acid (0.1N HCl), neutral and alkaline (0.1N NaOH) hydrolytic conditions at 80 degrees C, as well as to oxidative decomposition at room temperature. Photolysis was carried out in 0.1N HCl, water and 0.1N NaOH at 40 degrees C. Additionally, the solid drug was subjected to 50 degrees C for 60 days in a dri-bath, and to the combined effect of temperature and humidity, with and without light, at 40 degrees C/75% RH. The products formed under different stress conditions were investigated by LC and LC-MS. The LC method that could separate all degradation products formed under various stress conditions involved a C18 column and a mobile phase comprising of ACN and phosphate buffer (pH 3). The flow rate and detection wavelength were 1 ml min(-1) and 210 nm, respectively. The developed method was found to be precise, accurate, specific and selective. It was suitably modified for LC-MS studies by replacing phosphate buffer with water, where pH was adjusted to 3.0 with formic acid. The drug showed instability in solution state (under acidic, neutral, alkaline and photolytic stress conditions), but was relatively stable in the solid-state, except formation of minor products under accelerated conditions. Primarily, maximum degradation products were formed in acid conditions, though the same were also produced variably under other stress conditions. The LC-MS m/z values and fragmentation patterns of two of the five products matched with enalaprilat and diketopiperazine derivative, previously known degradation products of enalapril. Also, m/z value of another product matched with an impurity listed in the drug monograph in European Pharmacopoeia. Rest two were hitherto unknown degradation products. The products were characterized through LC-MS fragmentation studies. Based on the results, a more complete degradation pathway for the drug could be proposed.